Citations 2
Dose-dependent white matter changes associated with repetitive head impacts in former American football players
Arciniega, Hector , Wickham, Alana, Szekely, Brian, Kim, Nicholas, Cho, Kang I, Carrington, Holly, Knyazhanskaya, Evdokiya , John, Omar , Jung, Leonard , Breedlove, Katherine M. , Mirmajlesi, Anya S, Stearns, Jared, Rushmore, R Jarrett, Daneshvar, Daniel H, Wiegand, Tim L T, Billah, Tashrif , Pasternak, Ofer, Cetin-Karayumak, Suheyla, Rathi, Yogesh, Coleman, Michael J, Bernick, Charles, Balcer, Laura J, Im, Brian , Datta, Shae , Alosco, Michael L. , Lin, Alexander P, Cummings, Jeffrey L, Reiman, Eric M, Stern, Robert A, Shenton, Martha E, Bouix, Sylvain, Su, Yi, Chen, Kewei, Protas, Hillary, Boker, Connie, Au, Rhoda, Cantu, Robert C, Farrer, Lindsay, Helm, Robert, Katz, Douglas I, Kowall, Neil, Mez, Jesse, Mercier, Gustavo, Otis, James, Weller, Jason, Simkin, Irene, Andino, Alondra, Conneely, Shannon, Diamond, Courtney, Fagle, Tessa, Haller, Olivia, Hunt, Tennyson, Gullotti, Nicole, Mariani, Megan, Mayville, Brian, McLaughlin, Kathleen, Nanna, Mary, Platt, Taylor, Rice, Fiona, Sestak, Madison, McClean, Michael, Tripodis, Yorghos, Annis, Douglas, Chaisson, Christine, Dixon, Diane, Finney, Carolyn, Gallagher, Kerrin, Hartlage, Kaitlin , Lu, Jun, Martin, Brett, Ojo, Emmanuel, Palmisano, Joseph N, Pine, Brittany, Ramachandran, Janani, Fitzsimmons, Jennifer, Arcinieago, Hector, Bonke, Elena, Coello, Eduardo , Jung, Leonhard, Liao, Huijun, Loy, Maria, Rizzoni, Elizabeth, Schultz, Vivian , Silva, Annelise, Vessey, Brynn, Banks, Sarah, Miller, Jason, Ritter, Aaron , Sabbagh, Marwan, Cruz, Raelynn de la, Durant, Jan, Golceker, Morgan, Harmon, Nicolette, Kaylegian, Kaeson, Long, Rachelle, Nance, Christin, Sandoval, Priscilla, Serrano, Andrew, Dodick, David W, Geda, Yonas, Wethe, Jennifer V, Falk, Bryce, Duffy, Amy, Howard, Marci, Montague, Michelle , Osgood, Thomas, Babcock, Debra, Bellgowan, Patrick, Balcer, Laura, Barr, William, GOLDBERG, JUDITH, Wisniewski, Thomas, Kirov, Ivan, Lui, Yvonne, Marmar, Charles, Hasanaj, Lisena, Serrano, Liliana , Al-Kharafi, Alhassan, George, Allan, Martin, Sammie, Riley, Edward, Runge, William, Peskind, Elaine R. , Colasurdo, Elizabeth , Marcus, Daniel S, Gurney, Jenny , Greenwald, Richard, Johnson, Keith A, Wethe, Jennifer V. , Wiegand, Tim L. T. , Jung, Leonard B , Breedlove, Katherine , Stearns, Jared , Adler, C H , Alosco, Michael L , Koerte, Inga K , Wethe, Jennifer V , Arciniega, Hector , Kim, Nicholas , Carrington, Holly , Rushmore, R. Jarrett , Daneshvar, Daniel H. , Pasternak, Ofer , Karayumak, Suheyla Cetin , Rathi, Yogesh , Coleman, Michael J. , Adler, Charles H. , Bernick, Charles , Balcer, Laura J. , Reiman, Eric M. , Shenton, Martha E. , Bouix, Sylvain , Protas, Hillary , Cantu, Robert C. , Katz, Douglas I. , Mez, Jesse , Weller, Jason , Fagle, Tessa, Mariani, Megan, McLaughlin, Kathleen , Pulukuri, Surya Vamsi , Sestak, Madison, McClean, Michael D , Tripodis, Yorghos , Annis, Douglas, Finney, Carolyn, Palmisano, Joseph , Pine, Brittany, Ramachandran, Janani , Bonke, Elena M. , Liao, Huijun, II, Robert W. Turner , Marek, Kenneth , Dodick, David W. , Geda, Yonas E. , Howard, Marci, Montague, Michelle, Babcock, Debra, Bellgowan, Patrick S.F. , Barr, William , Kirov, Ivan, George, Allan, Colasurdo, Elizabeth A. , Marcus, Daniel S., Johnson, Keith A.
Brain Communications | May 29, 2026 | Volume: 8 | Issue: 3 | Pages: No page available
Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P < 0.00001) and an earlier age of first exposure to tackle football (P < 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P < 0.04) and rotational force (P < 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.
Alterations in CSF Amyloid-β and Tau Biomarkers in Former College and Professional American Football Players: Findings from the DIAGNOSE CTE Research Project
Shofer, Jane B. , Colasurdo, Elizabeth A. , Li, Ge , Adler, Charles H., Balcer, Laura, Bernick, Charles, Daneshvar, Daniel, Katz, Douglas I., McClean, M M, Mez, Jesse, Palmisano, Joseph, Ashton, Nicholas, Blennow, K., Zetterberg, Henrik, Tripodis, Yorghos, Alosco, Michael L., Cummings, Jeffrey L., Reiman, EM, Shenton, Martha, Stern, Robert A., Iliff, Jeffrey J. , Peskind, Elaine R. , Jansson, Deidre , Schindler, Abigail G. , Adler, Charles H. , Bernick, Charles , Daneshvar, Daniel H. , Katz, Douglas I. , McClean, Michael D , Mez, Jesse , Palmisano, Joseph , Ashton, Nicholas J. , Blennow, Kaj , Zetterberg, Henrik , Tripodis, Yorghos , Alosco, Michael L. , Cummings, Jeffrey L. , Reiman, Eric M. , Shenton, Martha E.
Journal of Neurotrauma | January 30, 2026 | Volume: 43 | Issue: 7-8 | Pages: 559-574
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHIs), characterized by tau tangles around small blood vessels at the depths of the sulci. Currently, CTE can be diagnosed only postmortem , but can present with an array of cognitive, behavioral, mood, and motor symptoms. However, traumatic brain injury is also associated with increased risk of Alzheimer’s disease (AD) and may lead to comorbid neuropathology. Characterization of the in vivo biomarkers of CTE is a necessary next step to facilitate accurate diagnoses. We examined the profile of cerebrospinal fluid (CSF) biomarkers of amyloid-β, total tau (tTau), and phospho-tau (pTau) in a cohort of former professional (PRO, n = 100) and college (COL, n = 40) football players at high risk of CTE compared to asymptomatic unexposed controls (UE, n = 43). CSF was collected under controlled conditions using collection, processing, and cryostorage kits provided by the DIAGNOSE CTE Research Project Biomarker Core, and concentrations of Aβ 40 , Aβ 42 , tTau, and pTau (pTau 181 , pTau 217 , pTau 231 ) were measured at the University of Gothenburg, Sweden, using immunoassays. Associations between CSF biomarker levels with football history, and diagnosis of traumatic encephalopathy syndrome (TES) were examined using linear regression, and corrected for age, education, APOE -ε4 allele status, race, and body mass index. Our analysis revealed that football exposure affected both CSF Aβ 40 ( p = 0.039) and Aβ 42 ( p = 0.038), particularly among those under 60 years of age in the PRO compared to the UE exposure group. Among former football players, estimates of RHI exposure were not generally associated with CSF Aβ, tTau, and pTau biomarker levels. CSF Aβ 40 ( p = 0.0041) and Aβ 42 ( p = 0.011) were lower in former football players with TES diagnosis compared to unexposed participants, although CSF Aβ, tTau, and pTau biomarker levels did not differ between former players with and without a TES diagnosis. Among former football players, reduced CSF Aβ 40 ( p = 0.011) and Aβ 42 (p = 6e-04) were observed in those with cognitive impairment compared to those with neurobehavioral dysregulation. The findings of significant associations of reduced CSF Aβ levels with RHI in elite football players are in line with recent postmortem studies; however, the lack of relationship with CSF tTau and pTau species observed to be altered in the setting of AD suggests that the pathological features of CTE reflected in fluid biomarkers are complex and require further study. The overlapping comorbid age-dependent features of neurodegeneration that occur in those at risk for CTE suggest that tau pathology in CTE is not reliably reflected by currently available fluid biomarkers and that the use of multiple biomarkers related to the compound characteristics of CTE may be required for early detection.